3-aryl-pyrrolidine-2,4-diones

ABSTRACT

An acylamino ester of the formula ##STR1## wherein X is C 1-6  alkyl, or halogen, 
     Y is hydrogen, C 1-6  alkyl, halogen, or C 1-3  halogenalkyl, 
     Z is C 1-6  alkyl, or halogen, 
     n is 0 to 3, 
     provided that when n is O,Y is not hydrogen, and 
     R 3  is C 1-6  alkyl.

This is a division of application Ser. No. 564,267, filed Aug. 8, 1990,now U.S. Pat. 5,091,537 which is a division of application Ser. No.391,227, filed Aug. 8, 1989, now U.S. Pat. No. 4,985,063.

The invention relates to new 3-aryl-pyrrolidine-2,4-dione (e)derivatives, a plurality of processes for their preparation, and theiruse as herbicides, fungicides, antimycotics, insecticides andacaricides.

Pharmaceutical properties have previously been described in3-acyl-pyrrolidine-2,4-diones (S. Suzuki and coworkers, Chem. Pharm.bull. 15 1120 (1967)). N-Phenylpyrrolidine-2,4-diones were furthermoresynthesized by R. Schmierer and H. Mildenberger Liebigs Ann. Chem. 19851095. A biological activity of these compounds has not been described.

In EP-A 0,262,399 there are published compounds of a similar structure(3-aryl-pyrrolidine-2,4-diones), but nothing has been known of thesecompounds about a herbicidal, fungicidal, antimycotic, tickicidal,insecticidal or acaricidal activity.

New 3-aryl-pyrrolidine-2,4-dione (e) derivatives have now been found,which are represented by the formula (I) ##STR2## in which X representsalkyl, halogen and alkoxy,

Y represents hydrogen, alkyl, halogen, alkoxy and halogenoalkyl,

Z represents alkyl, halogen and alkoxy,

m represents a number from 1-4,

n represents a number from 0-3,

R represents hydrogen or A, or represents the groups --CO--R¹,--CO--O--R²

where

A represents a metal cation equivalent or represents an ammonium ion,

R¹ represents optionally halogen-substituted alkyl, alkenyl,alkoxyalkyl, alkylthioalkyl, polyalkoxyalkyl and optionally substitutedcycloalkyl which can be interrupted by hetero atoms, or representsoptionally substituted phenyl, optionally substituted phenylalkyl,substituted hetaryl, substituted phenoxyalkyl and substitutedhetaryloxyalkyl and

R² represents optionally halogen-substituted alkyl, cycloalkyl, alkenyl,alkoxyalkyl, polyalkoxyalkyl and optionally substituted phenyl,

as well as the pure enantiomeric forms of compounds of the formula (I).

The following sub-groups may be defined below:

(Ia) Compounds of the formula (I) where R=hydrogen,

(Ib): Compounds of the formula (I) where R=COR¹,

(Ic): Compounds of the formula (I) where R=COOR²,

(Id): Compounds of the formula (I) where R=a metal ion equivalent or anammonium ion.

Furthermore, it has been found that 3-arylpyrrolidine-2,4-diones or theenols thereof, of the formula (Ia) ##STR3## are obtained when

(A)

N-acylamino acid esters of the formula (II) ##STR4## in which X, Y, Z, mand n have the meanings mentioned herein, and

R³ represents alkyl, preferably C₁ -C₆ -alkyl, are subjected to anintramolecular condensation reaction in the presence of a diluent and inthe presence of a base.

(B)

Furthermore, it has been found that compounds of the formula (Ib)##STR5## are obtained when compounds of the formula (Ia) ##STR6## inwhich X, Y, Z, m and n have the abovementioned meanings,

are reacted

α) with acid halides of the general formula (III) ##STR7## in which R¹has the abovementioned meaning and

Hal represents halogen, in particular chlorine and bromine,

if appropriate in the presence of a diluent and if appropriate in thepresence of an acid-binding agent,

or

β) with carboxylic anhydrides of the general formula (IV)

    R.sup.1 --CO--O--CO--R.sup.1                               (IV)

in which

R¹ has the abovementioned meaning,

if appropriate in the presence of a diluent and if appropriate in thepresence of an acid-binding agent.

(C)

Furthermore, it has been found that compounds of the formula (Ic)##STR8## are obtained when compounds of the formula (Ia) ##STR9## inwhich X, Y, Z, m and n have the abovementioned meanings

are reacted with chloroformic acid esters of the general formula (V)

    R.sup.2 --O--CO--Cl                                        (V)

in which

R² has the abovementioned meaning,

if appropriate in the presence of a diluent and if appropriate in thepresence of an acid-binding agent.

(D)

Furthermore, it has been found that compounds of the formula (Id)##STR10## in which X, Y, Z, A, m and n have the abovementioned meaningsare obtained when compounds of the formula (Ia) ##STR11## in which X, Y,Z, m and n have the abovementioned meanings, are reacted with metalhydroxides or amines of the general formulae (VIII) and (IX) ##STR12##in which Me represents monovalent or divalent metal ions,

s and t represent the number 1 and 2 and

R⁵, R⁶ and R⁷ independently of one another represent hydrogen and alkyl,

if appropriate in the presence of a diluent.

Surprisingly, it has been found that the new3-arylpyrrolidine-2,4-diones of the formula (I) are distinguished byoutstanding herbicidal, insecticidal, antimycotic and acaricidal effects

Preferred compounds are condensed1,5-alkylene-3-aryl-pyrrolidine-2,4-diones and the corresponding enolesters thereof, of the formula (I), in which

X represents C₁ -C₆ -alkyl, halogen and C₁ -C₆ -alkoxy,

Y represents hydrogen, C₁ -C₆ -alkyl, halogen, C₁ -C₆ -alkoxy and C₁ -C₃-halogenoalkyl,

Z represents C₁ -C₆ -alkyl, halogen and C₁ -C₆ -alkoxy,

m represents a number from 1-4,

n represents a number from 0-3,

R represents hydrogen (Ia), or represents the groups of the formula

    --CO--R.sup.1                                              (Ib),

    --CO--O--R.sup.2                                           (Ic)

or

    A                                                          (Id)

in which

A represents a metal cation equivalent or represents an ammonium ion,

R¹ represents optionally halogen-substituted: C₁ -C₂₀ -alkyl, C₂ -C₂₀-alkenyl, C₁ -C₈ -alkoxy-C₁ -C₈ -alkyl, C₁ -C₈ -alkylthio-C₁ -C₈ -alkyl,C₁ -C₈ -polyalkoxy-C₂ -C₈ -alkyl and cycloalkyl which has 3-8 ring atomsand which can be interrupted by oxygen and/or sulphur,

or represents optionally halogen-, nitro-, C₁ -C₆ -alkyl-, C₁ -C₆-alkoxy-, C₁ -C₆ -halogenoalkyl- or C₁ -C₆ -halogenoalkoxy-substitutedphenyl; or represents optionally halogen-, C₁ -C₆ -alkyl-, C₁ -C₆-alkoxy-, C₁ -C₆ -halogenoalkyl- or C₁ --C₆ halogenoalkoxy-substitutedphenyl-C₁ -C₆ -alkyl, or represents optionally halogen- and C₁ -C₆-alkyl-substituted hetaryl,

or represents optionally halogen- and C₁ -C₆ -alkyl-substitutedphenoxy-C₁ -C₆ -alkyl,

or represents optionally halogen-, amino- and C₁ -C₆ -alkyl-substitutedhetaryloxy-C₁ -C₆ -alkyl,

R² represents optionally halogen-substituted: C₁ -C₂₀ -alkyl, C₂ -C₂₀-alkenyl, C₁ -C₈ -alkoxy-C₂ -C₈ -alkyl and C₁ -C₈ -polyalkoxy-C₂ -C₈-alkyl, or represents halogen-, nitro-, C₁ -C₆ -alkyl-, C₁ -C₆ -alkoxy-,C₁ -C₆ -halogenoalkyl-substituted phenyl,

and the enantiomerically pure forms of compounds of the formula (I).

Particularly preferred compounds of the formula (I) are those in which

X represents C₁ -C₄ -alkyl, halogen and C₁ -C₄₃ -alkoxy,

Y represents hydrogen, C₁ -C₆ -alkyl, halogen, C₁ -C₄ -alkoxy and C₁ -C₂-halogenoalkyl,

Z represents C₁ -C₄ -alkyl, halogen and C₁ -C₄ -alkoxy,

m represents a number from 1-3,

n represents a number from 0-3,

R represents hydrogen (Ia), or represents the groups of the formula

    --CO--R.sup.1                                              (Ib),

    --CO--O--R.sup.2                                           (Ic)

or,

    A                                                          (Id)

in which

A represents a metal cation equivalent or represents an ammonium ion,

R¹ represents optionally halogen-substituted: C₁ -C₁₆ -alkyl, C₂ -C₁₆-alkenyl, C₁ -C₆ -alkoxy-C₁ -C₆ -alkyl, C₁ -C₆ -alkylthio-C₁ -C₆ -alkyl,C₁ -C₆ -polyalkoxy-C₂ -C₆ -alkyl and cycloalkyl which has 3-7 ring atomsand which can be interrupted by 1-2 oxygen and/or sulphur atoms,

or represents optionally halogen-, nitro-, C₁ -C₄ -alkyl-, C₁ -C₄-alkoxy-, C₁ -C₃ -halogenoalkyl- or C₁ -C₃ -halogenoalkoxy-substitutedphenyl,

or represents optionally halogen-, C₁ -C₄ -alkyl-, C₁ -C₄ -alkoxy-, C₁-C₃ -halogenoalkyl- or C₁ -C₃ -halogenoalkoxy-substituted phenyl-C₁ -C₄-alkyl,

or represents optionally halogen- and C₁ -C₆ -alkyl-substituted hetaryl,

or represents optionally halogen- and C₁ -C₄ -alkyl-substitutedphenoxy-C₁ -C₅ -alkyl,

or represents optionally halogen-, amino- and C₁ -C₄ -alkyl-substitutedhetaryloxy-C₁ -C₁ -alkyl,

R² represents optionally halogen-substituted: C₁ -C₁₆ -alkyl, C₂ -C₁₆-alkenyl, C₁ 2-C₁₆ -alkoxy-C₂ -C₆ -alkyl and C₁ -C₆ -polyalkoxy-C₂ -C₆-alkyl, or represents halogen-, nitro-, C₁ -C₄ -alkyl-, C₁ -C₃ -alkoxy-or C₁ -C₃ -halogenoalkyl-substituted phenyl,

and the enantiomerically pure forms of compounds of the formula (I).

Very particularly preferred compounds of the formula (I}are those inwhich

X represents methyl, ethyl, propyl, i-propyl, fluorine, chlorine,bromine, methoxy and ethoxy,

Y represents hydrogen, methyl, ethyl, propyl, ipropyl, butyl, i-butyl,tert.-butyl, chlorine, bromine, methoxy, ethoxy and trifluoromethyl,

Z represents methyl, ethyl, i-propyl, butyl, i-butyl, tert.-butyl,chlorine, bromine, methoxy and ethoxy,

m represents a number from 1-2,

n represents a number from 0-3,

R represents hydrogen (Ia), or represents the groups of the formula

    --CO--R.sup.1                                              (Ib),

    --CO--O--R.sup.2                                           (Ic)

or

    A                                                          (Id)

in which

A represents a metal cation equivalent or represents an ammonium ion,

R¹ represents optionally fluorine- or chlorine-substituted: C₁ -C₁₄-alkyl, C₂ -C₁₄ -alkenyl, C₁ -C₄ -alkoxy-C₁ -C₆ -alkyl, C₁ -C₄-alkylthio-C₁ -C₆ -alkyl, C₁ -C₄ -polyalkoxyl-C₂ -C₄ -alkyl andcycloalkyl which has 3-6 ring atoms and which can be interrupted by 1-2oxygen and/or sulphur atoms, or represents optionally fluorine-,chlorine-, bromine-, methyl-, ethyl-, propyl-, i-propyl-, methoxy-,ethoxy-, trifluoromethyl-, trifluoromethoxy- or nitro-substitutedphenyl, or represents optionally fluorine-, chlorine-, bromine-,methyl-, ethyl-, propyl-, i-propyl-, methoxy-, ethoxy-, trifluoromethyl-or trifluoromethoxy-substituted phenyl-C₁ -C₃ -alkyl, or representsoptionally fluorine-, chlorine-, bromine-, methyl- or ethyl-substitutedpyridyl, pyrimidyl, thiazolyl and pyrazolyl, or represents optionallyfluorine-, chlorine-, methyl- or ethyl-substituted phenoxy-C₁ -C₄-alkyl, or represents optionally fluorine-, chlorine-, amino-, methyl-or ethyl-substituted pyridyloxy-C₁ -C₄ -alkyl, pyrimidyloxy-C₁ -C₄-alkyl and thiazolyloxy-C₁ -C₄ -alkyl,

R² represents optionally fluorine- or chlorine-substituted: C₁ -C₁₄-alkyl, C₂ -C₁₄ -alkenyl, C₁ -C₄ -alkoxy-C₂ -C₆ -alkyl and C₁ -C₄-polyalkoxy-C₂ -C₆ -alkyl, or represents optionally fluorine-,chlorine-, nitro-, methyl-, ethyl-, propyl-, i-propyl-, methoxy-,ethoxy- or trifluoromethyl-substituted phenyl,

as well as the enantiomerically pure forms of compounds of the formulaI.

If, according to process (A), ethylN-(2,6-dichlorophenylacetyl)-piperidine-2-carboxylate is used, thecourse of the process according to the invention can be represented bythe following equation: ##STR13##

If, according to process (B) (variant α),3-(2,4,6-trimethylphenyl)-1,5-trimethylene-pyrrolidine-2,4-dione andpivaloyl chloride are used as starting substance, the course of theprocess according to the invention can be represented by the followingequation: ##STR14##

If, according to process B (variant β),3-(2,4,5-trimethylphenyl)-1,5-tetramethylene-pyrrolidine-2,4-dione andacetic anhydride are used, the course of the process according to theinvention can be represented by the following equation. ##STR15##

If, according to process (C),3-(2,4-dichlorophenyl)-1,5-tetramethylene-pyrrolidine-2,4-dioneandethoxyethylchloroformate are used, the course of the process according to theinvention can be represented by the following equation. ##STR16## If,according to process (D),3-(2,4,6-trimethylphenyl)-1,5-trimethylene-pyrrolidine-2,4-dione andNaOH are used, the course of the process according to the invention canbe represented by the following equation: ##STR17##

The compounds required as starting substances in the above process (A),of the formula (II) ##STR18## in which X, Y, Z, m, n and R³ have theabovementioned meanings, were hitherto unknown, but can be prepared in asimple manner by methods which are known in principle. Thus, forexample, acyl-amino acid esters of the formula (II) are obtained when

a) amino acid esters of the formula (VI) ##STR19## in which R³represents alkyl and

m represents the number 1 or 2

are acylated with phenylacetic acid halides of the formula (VII)##STR20## in which X, Y, Z and n have the abovementioned meaning and

Hal represents chlorine or bromine,

(general methodology described in: Chem. Reviews 52 237-416 (1953)); orwhen

b) acylamino acids of the formula (IIa), ##STR21## in which X, Y, Z, mand n have the abovementioned meaning and

R⁴ represents hydrogen,

are esterified (general methodology described in: Chem. Ind. (London)1568 (1968)).

For example, compounds of the formula (IIa) can be obtained from thephenylacetic acid halides of the formula (VII) and amino acids of theformula (VIa) ##STR22## in which m represents the number 1 or 2,

by the method of Schotten-Baumann (Organikum [Laboratory Practical ofOrganic Chemistry] 9th edition 446 (1970) VEB Deutscher Verlag derWissenschaften, Berlin).

The following compounds of the formula (II) may be mentioned by way ofexample:

1) Ethyl N-(2,4-dichlorophenylacetyl-)-piperidine-2-carboxylate

2) Ethyl N-(2-fluoro-4-chlorophenylacetyl)-piperidine-2-carboxylate

3) Ethyl N-(2,6-dichlorophenylacetyl)-piperidine-2-carboxylate

4) Ethyl N-(2-fluoro-6-chlorophenylacetyl)-piperidine-2-carboxylate

5) Ethyl N-(2,4,6-trimethylphenylacetyl)-piperidine-2-carboxylate

6) EthylN-(2-fluoro-6-chloro-4-trifluoromethylphenylacetyl)-piperidine-2-carboxylate

7) EthylN-(2,6-dichloro-4-trifluoromethylphenylacetyl)-piperidine-2-carboxylate

8) Ethyl N-(2,4,5-trimethyl-phenylacetyl)-piperidine-2-carboxylate

9) EthylN-(2-fluoro-5-chloro-4-trifluoromethyl-phenylacetyl)-piperidine-2-carboxylate

10) Ethyl N-(2,4,6-triisopropyl-phenylacetyl-)-piperidine-2-carboxylate

11) Ethyl N-(2,4,6-trichlorophenylacetyl)-piperidine-2-carboxylate

12) Ethyl N-(2-chloro-3-methyl-phenylacetyl)-piperidine-2-carboxylate

13) EthylN-(3-bromo-2,4,6-trimethyl-phenylacetyl)-piperidine-2-carboxylate

14) Ethyl N-(pentamethyl-phenylacetyl)-piperidine-2-carboxylate

15) EthylN-(4-tert.-butyl-2-methyl-phenylacetyl)-piperidine-2-carboxylate

16) EthylN-(4-tert.-butyl-2,6-dimethyl-phenylacetyl)-piperidine-2-carboxylate

17) Ethyl N-(2,3,4,6-tetramethyl-phenylacetyl)-piperidine-2-carboxylate

18) Ethyl N-(2,3,6-trichloro-pehnylacetyl)-piperidine-2-carboxylate

19) Ethyl N-(2,4-dimethyl-phenylacetyl)-piperidine-2-carboxylate

20) Ethyl N-(2,3,4,5-tetramethyl-phenylacetyl)-piperidine-2-carboxylate

21) Ethyl N-(2,3,5,6-tetramethyl-phenylacetyl)-piperidine-2-carboxylate

22) EthylN-(2-fluoro-4,6-dimethyl-phenylacetyl)-piperidine-2-carboxylate

23) EthylN-(4-fluoro-2,6-dimethyl-phenylacetyl)-piperidine-2-carboxylate

24) Methyl N-(2,4-dichloro-phenylacetyl)-pyrrolidine-2-carboxylate

25) Methyl N-(2,6-dichloro-phenylacetyl)-pyrrolidine-2-carboxylate

26) Methyl N-(2,4,6-trimethyl-phenylacetyl)-pyrrolidine-2-carboxylate

27) Methyl N-(2,4,5-trimethyl-phenylacetyl)-pyrrolidine-2-carboxylate

28) Methyl N-(2-fluoro-6-chloro-phenylacetyl)-pyrrolidine-2-carboxylate

29) MethylN-(2,6-dichloro-4-trifluoromethyl-phenylacetyl)-pyrrolidine-2-carboxylate

30) Methyl N-(2,4,6-trichloro-phenylacetyl)-pyrrolidine-2-carboxylate

31) Methyl N-(2,3,6-trichloro-phenylacetyl)-pyrrolidine-2-carboxylate

32) MethylN-(2-fluoro-4,6-dimethyl-phenylacetyl)-pyrrolidine-2-carboxylate

33) MethylN-(4-fluoro-2,6-dimethyl-phenylacetyl)-pyrrolidine-2-carboxylate.

The following compounds of the formula (IIa) may be mentioned by way ofexample:

34) N-2,4-Dichlorophenylacetyl-prolinee

35) N-2-Fluoro-6-chlorophenylacetyl-prolinee

36) N-2,6-Dichlorophenylacetyl-prolinee

37) N-2,4,6-Trimethylphenylacetyl-prolinee

38) N-2,4,5-trimethylphenylacetyl-prolinee

39) N-2,6-Dichloro-4-trifluoromethyl-phenylacetyl-prolinee.

When carrying out process (A) according to the invention, the reactiontemperatures can be varied within a relatively wide range. In general,the process is carried out at temperatures between 0° C. and 250° C.,preferably between 50° C. and 150° C.

Process (A) according to the invention is generally carried out underatmospheric pressure.

When carrying out process (A) according to the invention, the reactantsof the formulae (II) and the deprotonating bases are generally employedin approximately equimolar amounts. However, it is also possible to useone or the other component in a relatively large excess (up to 3 moles).

Process (A) is characterized in that compounds of the formula (II) inwhich X, Y, Z, m, n and R: have the abovementioned meanings aresubjected to intramolecular condensation in the presence of bases.

Diluents which can be employed in process (A) according to the inventionare all customary inert organic solvents. Hydrocarbons, such ascyclohexane, toluene and xylene, furthermore ethers, such as dibutylether, tetrahydrofuran, dioxane, glycol dimethyl ether and diglycoldimethyl ether, and moreover polar solvents, such as dimethylsulphoxide, sulpholane, dimethylformamide and N-methyl-pyrrolidone, canpreferably be used.

Deprotonating agents which can be employed in carrying out process (A)according to the invention are all customary proton acceptors. Theoxides, hydroxides and carbonates of alkali metals and alkaline earthmetals, such as sodium hydroxide, potassium hydroxide, magnesium oxide,calcium oxide, sodium carbonate, potassium carbonate and calciumcarbonate, which can also be employed in the presence of phase transfercatalysts, such as, for example, triethylbenzylammonium chloride,tetrabutylammonium bromide, Adogen 464 or TDA 1, can preferably be used.Amides and hydrides of alkali metals and alkaline earth metals, such assodium amide, sodium hydride and calcium hydride, and, moreover, alsoalkali metal alkoxides, such as sodium methoxide, sodium methoxide andpotassium tert.-butoxide, can furthermore be employed.

Process (Bα) is characterized in that compounds of the formula (Ia) arereacted with carboxylic acid halides of the formula (III).

When the acid halides are used, diluents which can be employed inprocess (Bα) according to the invention are all solvents which are inerttowards these compounds. Hydrocarbons, such as benzine, benzene,toluene, xylene and tetralin, furthermore halogenohydrocarbons, such asmethylene chloride, chloroform, carbon tetrachloride, chlorobenzene ando-dichlorobenzene, moreover ketones, such as acetone and methylisopropyl ketone, furthermore ethers, such as diethyl ether,tetrahydrofuran and dioxane, and in addition carboxylic acid esters,such as ethyl acetate, and also strongly polar solvents, such asdimethyl sulphoxide and sulpholane, can preferably be used. If thestability of the acid halide to hydrolysis permits, the reaction canalso be carried out in the presence of water.

Suitable acid-binding agents for the reaction of process (Bα) accordingto the invention are all customary acid acceptors if the correspondingcarboxylic acid halides are used. Tertiary amines, such astriethylamine, pyridine, DABCO, DBU, DBA, Hunig base andN,N-dimethylaniline, furthermore alkaline earth metal oxides, such asmagnesium oxide and calcium oxide, moreover alkali metal carbonates andalkaline earth metal carbonates, such as sodium carbonate, potassiumcarbonate and calcium carbonate, can preferably be used.

When carrying out process (Bα) according to the invention, the reactiontemperatures can also be varied within a relatively wide range, evenwhen carboxylic acid halides are used. In general, the process iscarried out at temperatures between -20° C. and +150° C., preferablybetween 0° C. and 100° C.

When carrying out process (Bα) according to the invention, the startingsubstances of the formula (Ia) and the carboxylic acid halide of theformula (III) are generally used in approximately equimolar amounts.However, it is also possible to employ the carboxylic acid anhydride ina relatively large excess (up to 5 moles). Working-up is carried out bycustomary methods.

Process (Bβ) is characterized in that compounds of the formula (Ia) arereacted with carboxylic acid hydrides of the formula (IV).

If in process (Bβ) according to the invention carboxylic anhydride isused as the reactant for the formula (IV), it is possible to use asdiluents preferably those diluents which are also preferably suitablewhen acid halides are used. Alternatively, carboxylic acid hydride whichis employed in excess can also act simultaneously as the diluent.

In process (Bβ), according to the invention, the reaction temperaturescan also be varied within a relatively wide range even when carboxylicanhydrides are used. In general, the process is carried out attemperatures between -20° C. and +150° C., preferably between 0° C. and100° C.

When carrying out the process according to the invention, the startingsubstances of the formula (Ia) and the carboxylic anhydride of theformula (IV) are generally used in approximately equivalent amounts.However, it is also possible to employ the carboxylic anhydride in arelatively large excess (up to 5 moles). Working-up is carried out bycustomary methods.

In general, a procedure is followed in which the diluent and thecarboxylic anhydride, which is present in excess, as well as thecarboxylic acid which forms, are removed by distillation or by washingwith an organic solvent or using water.

Process (C) is characterized in that compounds of the formula (Ia) arereacted with chloroformic acid esters of the formula (V).

If the corresponding chloroformic acid esters are used, suitableacid-binding agents in the reaction of process (C) according to theinvention are all customary acid acceptors. Tertiary amines, such astriethylamine, pyridine, DABCO, DBC,, DBA, Hunig base andN,N-dimethylaniline, furthermore alkaline earth metal oxides, such asmagnesium oxide and calcium oxide, moreover alkali metal carbonates andalkaline earth metal carbonates, such as sodium carbonate, potassiumcarbonate and calcium carbonate, can preferably be used.

When the chloroformic acid esters are used, diluents which can beemployed in process (C) according to the invention are all solventswhich are inert towards these compounds. Hydrocarbons, such as benzine,benzene, toluene, xylene and tetralin, furthermore halogenohydrocarbons,such as methylene chloride, chloroform, carbon tetrachloride,chlorobenzene and o-dichlorobenzene, moreover ketones, such as acetoneand methyl isopropyl ketone, furthermore ethers, such as diethyl ether,tetrahydrofuran and dioxane, and in addition carboxylic acid esters,such as ethyl acetate, and also strongly polar solvents, such asdimethyl sulphoxide and sulpholane, preferably be used.

When carrying out process (C) according to the invention, the reactiontemperatures can be varied within a relatively wide range when thechloroformic acid esters are used as the carboxylic acid derivatives ofthe formula (V). If the process is carried out in the presence of adiluent and of an acid-binding agent, the reaction temperaturesgenerally are between -20° C. and +100° C., preferably between 0° C. and50° C.

Process (C) according to the invention is generally carried out underatmospheric pressure.

When carrying out process (C) according to the invention, the startingsubstances of the formula (Ia) and the corresponding chloroformic acidester of the formula (V) are generally used in approximately equivalentamounts. However, it is also possible to employ one or the othercomponent in a relatively large excess (up to 2 moles). Working-up isthen carried out by customary methods. In general, a procedure isfollowed in which the precipitated salts are removed and the reactionmixture which remains is concentrated by stripping off the solvent.

Process (D) is characterized in that compounds of the formula (Ia) arereacted with acetal hydroxides (VIII) or amines (IX).

Diluents which can be employed in the process according to the inventionare preferably ethers, such as tetrahydrofuran, dioxane or diethylether, and also alcohols, such as methanol, ethanol or isopropanol, andalso water. Process (D) according to the invention is generally carriedout under atmospheric pressure. The reaction temperatures are generallybetween -20° C. and 100° C., preferably between 0° C. and 50° C.

When carrying out process (D) according to the invention, the startingsubstances of the formula (Ia) or (IX) are generally used inapproximately equimolar amounts. However, it is also possible to employone or the other component in a relatively large excess (up to 2 moles).In general, a procedure is followed in which the reaction mixture isconcentrated by stripping off the diluent.

EXAMPLE 1 ##STR23##

8.4 g (0.28 mol) of sodium hydride (80% strength) are introduced into150 ml of absolute toluene. After 80 g (0.23 mol) of ethylN-(2,6-dichlorophenylacetyl)-piperidine-2-carboxylate in 400 ml ofabsolute toluene have been added dropwise, the mixture is refluxed for 6hours. 30 ml of ethanol are added dropwise while cooling in an ice bath,the batch is evaporated in vacuo on a rotary evaporator, the residue isdissolved in 1N NaOH, and3-(2,6-dichlorophenyl)-1,5-tetramethylene-pyrrolidine-2,4-dione isprecipitated at 0°-20° C. using concentrated HCl. For purification, theproduct is boiled with chloroform, n-hexane is then added, and thecolourless product which has precipitated is filtered off with suction.

Yield: 40.5 g (59.1% of theory) M.p. >250° C.

EXAMPLE 2 ##STR24##

4.6 g (15 mmol) of3-(2,4,6-trimethylphenyl)-1,5-tetramethylene-pyrrolidine-2,4-dione aresuspended in 50 ml of absolute THF, and the mixture is treated with 1.22ml (15 mmol) of absolute pyridine and 2.54 ml (15 mmol) ofethyl-diisopropylamine. 1.94 ml (15 mmol) of 3-chloro-pivaloyl chloride,dissolved in 5 ml of absolute THF, are added dropwise at 0°-10° C. tothis mixture, followed by stirring for 30 minutes. The precipitate isfiltered off, the solution is evaporated in vacuo on a rotaryevaporator, and the residue is chromatographed on silica gel usingcyclohexane/ethyl acetate 1:1.

Crystallization from ether/n-hexane gives 3.93 g (70% of theory) of4-(3-chloropivaloyloxy)-3-(2,4,6-trimethylphenyl)-1,5-tetramethylene-3-pyrrolin-2-oneof melting point 102° C.

EXAMPLE 3 ##STR25##

4.47 g (15 mmol) of3-(2,4-dichlorophenyl)1,5-tetramethylenepyrrrolidine-2,4-dione in 50 mlof absolute THF are treated with 1.22 ml (15 mmol) of absolute pyridine.2.44 g (15 mmol) of ethoxyethyl chloroformate, dissolved in 5 ml ofabsolute THF, are added dropwise at 0°-10° C., followed by stirring for30 minutes. After the precipitate has been filtered off, the filtrate isevaporated in vacuo on a rotary evaporator, and the residue ischromatographed on silica gel using cyclohexane/ethyl acetate 1:2 andcrystallized from ether/nhexane.

Yield: 5.2 g (83.7% of theory) of4-ethoxyethyloxycarbonyloxy-3-(2,4-dichlorophenyl)-1,5-tetramethylene-3-pyrrolin-2-oneof melting point 80° C.

The 3-aryl-pyrrolidin-2,4-dione (e) derivatives of the formula(Ia)-(Ic), which are listed by their formulae in Tables 1-3 below, areobtained in a manner corresponding to the Preparation Examples andfollowing the general preparation instructions.

                  TABLE 1                                                         ______________________________________                                         ##STR26##                    (Ia)                                            Example No.                                                                            X       Y       Z.sub.n  m    M.P. °C.                        ______________________________________                                         4       Cl      Cl      --       1    >218                                    5       Cl      H       6-Cl     1    >230                                    6       CH.sub.3                                                                              CH.sub.3                                                                              5-CH.sub.3                                                                             1     228                                    7       CH.sub.3                                                                              CH.sub.3                                                                              6-CH.sub.3                                                                             1    >230                                    8       Cl      H       --       2     174                                    9       F       Cl      --       2     207                                   10       Cl      Cl      --       2     208                                   11       Cl      H       6-F      2     230                                   12       CH.sub.3                                                                              CH.sub.3                                                                              5-CH.sub.3                                                                             2     210                                   13       CH.sub.3                                                                              CH.sub.3                                                                              6-CH.sub.3                                                                             2    >230                                   14       F       CF.sub.3                                                                              5-F      2     228                                   15       F       CF.sub.3                                                                              5-Cl     2    >230                                   16       F       CF.sub.3                                                                              6-Cl     2     227                                   17       Cl      CF.sub.3                                                                              6-Cl     2    >230                                   18       CH.sub.3                                                                              H       6-CH.sub.3                                                                             2                                           19       CH.sub.3                                                                              H       6-Cl     2                                           20       CH.sub.3                                                                              CH.sub.3                                                                              3-CH.sub.3                                                                             2                                           21       CH.sub.3                                                                              CH.sub.3                                                                              3.5-di-CH.sub.3                                                                        2     160                                   22       CH.sub.3                                                                              CH.sub.3                                                                              3.5.6-tri-CH.sub.3                                                                     2    >230                                   23       CH.sub.3                                                                              t-C.sub.4 H.sub.9                                                                     6-CH.sub.3                                                                             2    >230                                   24       CH.sub.3                                                                              F       --       2     191                                   25       CH.sub.3                                                                              CH.sub.3                                                                              --       2     192                                   26       CH.sub.3                                                                              t-C.sub.4 H.sub.9                                                                     --       2     210                                   27       Cl      H       3-CH.sub.3                                                                             2     195                                   28       Cl      H       3.5-di-Cl                                                                              2    >230                                   29       Cl      Cl      6-Cl     2    >230                                   30       CH.sub.3                                                                              F       6-CH.sub.3                                                                             2    >230                                   31       CH.sub.3                                                                              CH.sub.3                                                                              6-F      2     207                                   32       i-C.sub.3 H.sub.7                                                                     i-C.sub.3 H.sub.7                                                                     6-i-C.sub.3 H.sub.7                                                                    2    >230                                   33       CH.sub.3                                                                              H       3.5.6-tri-CH.sub.3                                                                     2    >230                                   34       CH.sub.3                                                                              CH.sub.3                                                                              3.6-di-CH.sub.3                                                                        2    >230                                   35       CH.sub.3                                                                              CH.sub.3                                                                              3-Br-6-CH.sub.3                                                                        2    >230                                   ______________________________________                                    

                                      TABLE 2                                     __________________________________________________________________________     ##STR27##                                (Ib)                                Example                                                                       No.  X   Y   Z.sub.n                                                                              m R.sup.1           M.P. °C.                       __________________________________________________________________________     36  Cl  Cl  --     1 CH.sub.3           95                                    37  Cl  Cl  --     1 (CH.sub.3).sub.2 CH                                                                             Oil                                    38  Cl  Cl  --     1 (CH.sub.3).sub.3 C                                                                              Oil                                    39  Cl  Cl  --     1 (CH.sub.3).sub.2CHC(CH.sub.3).sub.2                                                             Oil                                    40  Cl  H   6-Cl   1 CH.sub.3           80                                    41  Cl  H   6-Cl   1 (CH.sub.3).sub.2 CH                                      42  Cl  H   6-Cl   1 (CH.sub.3).sub.3 C                                                                              102                                    43  Cl  H   6-Cl   1 (CH.sub.3).sub.2 CHC(CH.sub.3).sub.2                                                            Oil                                    44  Cl  H   6-Cl   1 (CH.sub.3).sub.3 CCH.sub.2                                                                      Oil                                    45  Cl  H   6-Cl   1 (CH.sub.3).sub.2 CCH                                                                            Oil                                    46  Cl  H   6-Cl   1                                                                                ##STR28##         85                                    47  Cl  H   6-Cl   1                                                                                ##STR29##         98                                    48  Cl  H   6-Cl   1                                                                                ##STR30##        143                                    49  CH.sub.3                                                                          CH.sub.3                                                                          5-CH.sub.3                                                                           1 CH.sub.3          Oil                                    50  CH.sub.3                                                                          CH.sub.3                                                                          5-CH.sub.3                                                                           1 (CH.sub.3).sub.2 CH                                      51  CH.sub.3                                                                          CH.sub.3                                                                          5-CH.sub.3                                                                           1 (CH.sub.3).sub.3 C                                                                              Oil                                    52  CH.sub.3                                                                          CH.sub.3                                                                          5-CH.sub.3                                                                           1 (CH.sub.3).sub.2 CHC(CH.sub.3).sub.2                     53  CH.sub.3                                                                          CH.sub.3                                                                          6-CH.sub.3                                                                           1 CH.sub.3          Oil                                    54  CH.sub.3                                                                          CH.sub.3                                                                          6-CH.sub.3                                                                           1 (CH.sub.3).sub.2 CH                                                                             Oil                                    55  CH.sub.3                                                                          CH.sub.3                                                                          6-CH.sub.3                                                                           1 (CH.sub.3).sub.3 C                                                                              Oil                                    56  CH.sub.3                                                                          CH.sub.3                                                                          6-CH.sub.3                                                                           1 (CH.sub.3).sub.2 CH(CH.sub.3).sub.2C                                                            Oil                                    57  CH.sub.3                                                                          CH.sub.3                                                                          6-CH.sub.3                                                                           1                                                                                ##STR31##        Oil                                    58  CH.sub.3                                                                          CH.sub.3                                                                          6-CH.sub.3                                                                           1 (CH.sub.3).sub.3 CCH.sub.2                                                                      Oil                                    59  CH.sub.3                                                                          CH.sub.3                                                                          6-CH.sub.3                                                                           1 CH.sub.2CH(CH.sub.2).sub.7                                                                      Oil                                    60  CH.sub.3                                                                          CH.sub.3                                                                          6-CH.sub.3                                                                           1 (CH.sub.3).sub.2CHCH.sub.2                                                                      Oil                                    61  CH.sub.3                                                                          CH.sub.3                                                                          6-CH.sub.3                                                                           1                                                                                ##STR32##        Oil                                    62  CH.sub.3                                                                          CH.sub.3                                                                          6-CH.sub.3                                                                           1                                                                                ##STR33##        Oil                                    63  CH.sub.3                                                                          CH.sub.3                                                                          6-CH.sub.3                                                                           1                                                                                ##STR34##        105                                    64  CH.sub.3                                                                          CH.sub.3                                                                          6-CH.sub.3                                                                           1                                                                                ##STR35##        Oil                                    65  CH.sub.3                                                                          CH.sub.3                                                                          6-CH.sub.3                                                                           1                                                                                ##STR36##        Oil                                    66  CH.sub.3                                                                          CH.sub.3                                                                          6-CH.sub.3                                                                           1                                                                                ##STR37##        Oil                                    67  CH.sub.3                                                                          CH.sub.3                                                                          6-CH.sub.3                                                                           1                                                                                ##STR38##        Oil                                    68  CH.sub.3                                                                          CH.sub.3                                                                          6-CH.sub.3                                                                           1 H.sub.3 CSCH.sub.2                                                                              105                                    69  CH.sub.3                                                                          CH.sub.3                                                                          6-CH.sub.3                                                                           1                                                                                ##STR39##        Oil                                    70  CH.sub.3                                                                          CH.sub.3                                                                          6-CH.sub.3                                                                           1                                                                                ##STR40##        Oil                                    71  CH.sub.3                                                                          CH.sub.3                                                                          6-CH.sub.3                                                                           1                                                                                ##STR41##        120                                    72  CH.sub.3                                                                          CH.sub.3                                                                          6-CH.sub.3                                                                           1                                                                                ##STR42##        Oil                                    73  CH.sub.3                                                                          CH.sub.3                                                                          6-CH.sub.3                                                                           1                                                                                ##STR43##        115                                    74  CH.sub.3                                                                          CH.sub.3                                                                          6-CH.sub.3                                                                           1                                                                                ##STR44##        106                                    75  CH.sub.3                                                                          CH.sub.3                                                                          6-CH.sub.3                                                                           1                                                                                ##STR45##        120                                    76  CH.sub.3                                                                          CH.sub.3                                                                          6-CH.sub.3                                                                           1                                                                                ##STR46##        oil                                    77  CH.sub.3                                                                          CH.sub.3                                                                          6-CH.sub.3                                                                           1                                                                                ##STR47##        Oil                                    78  CH.sub.3                                                                          CH.sub.3                                                                          6-CH.sub.3                                                                           1                                                                                ##STR48##         73                                    79  CH.sub.3                                                                          CH.sub.3                                                                          6-CH.sub.3                                                                           1                                                                                ##STR49##        118                                    80  CH.sub.3                                                                          CH.sub.3                                                                          6-CH.sub.3                                                                           1                                                                                ##STR50##        108                                    81  CH.sub.3                                                                          CH.sub.3                                                                          6-CH.sub.3                                                                           1                                                                                ##STR51##        Oil                                    82  CH.sub.3                                                                          CH.sub.3                                                                          6-CH.sub.3                                                                           1                                                                                ##STR52##        122                                    83  CH.sub.3                                                                          CH.sub.3                                                                          6-CH.sub.3                                                                           1                                                                                ##STR53##        102                                    84  CH.sub.3                                                                          CH.sub.3                                                                          6-CH.sub.3                                                                           1                                                                                ##STR54##        Oil                                    85  Cl  Cl  --     2 CH.sub.3          120                                    86  Cl  Cl  --     2 (CH.sub.3).sub.2 CH                                                                              68                                    87  Cl  Cl  --     2 (CH.sub.3).sub.3 C                                                                               94                                    88  Cl  Cl  --     2 (CH.sub.3).sub.2 CHC(CH.sub.3).sub.2                                                             62                                    89  Cl  Cl  --     2                                                                                ##STR55##        Oil                                    90  Cl  Cl  --     2                                                                                ##STR56##        125                                    91  Cl  H   6-Cl   2 CH.sub.3          120                                    92  Cl  H   6-Cl   2 (CH.sub.3).sub.2 CH                                                                              82                                    93  Cl  H   6-Cl   2 (CH.sub.3).sub.3 C                                                                              110                                    94  Cl  H   6-Cl   2 (CH.sub.3).sub.2 CHC(CH.sub.3).sub.2                                                             92                                    95  Cl  H   6-Cl   2 CH.sub.3SCH.sub.2 126                                    96  Cl  H   6-Cl   2                                                                                ##STR57##        150                                    97  Cl  H   6-Cl   2                                                                                ##STR58##        150                                    98  Cl  H   6-Cl   2                                                                                ##STR59##        106                                    99  Cl  H   6-Cl   2                                                                                ##STR60##        162                                   100  Cl  H   6-Cl   2                                                                                ##STR61##        130                                   101  Cl  H   6-Cl   2                                                                                ##STR62##        107                                   102  Cl  H   6-Cl   2                                                                                ##STR63##        107                                   103  Cl  H   6-Cl   2 (H.sub.3 COCH.sub.2).sub.3 C                                                                    105                                   104  Cl  H   6-Cl   2                                                                                ##STR64##        126                                   105  Cl  H   6-Cl   2                                                                                ##STR65##        114                                   106  Cl  H   6-Cl   2                                                                                ##STR66##        Oil                                   107  Cl  H   6-Cl   2                                                                                ##STR67##        136                                   108  Cl  H   6-Cl   2                                                                                ##STR68##        Oil                                   109  Cl  H   6-Cl   2 (CH.sub.3).sub. 3 CCH.sub.2                                                                     Oil                                   110  Cl  H   6-Cl   2                                                                                ##STR69##        122                                   111  Cl  H   6-Cl   2 CH.sub.2CH(CH.sub.2).sub.7                                                                      Oil                                   112  Cl  H   6-Cl   2                                                                                ##STR70##        Oil                                   113  Cl  H   6-Cl   2                                                                                ##STR71##                                              114  Cl  H   6-F    2 CH.sub.3          Oil                                   115  Cl  H   6-F    2 (CH.sub.3).sub.3 C                                                                              102                                   116  CH.sub.3                                                                          CH.sub.3                                                                          --     2 CH.sub.3          Oil                                   117  CH.sub.3                                                                          CH.sub.3                                                                          --     2 (CH.sub.3).sub.2 CH                                                                             Oil                                   118  CH.sub.3                                                                          CH.sub.3                                                                          --     2 (CH.sub.3).sub.3 C                                                                               65                                   119  CH.sub.3                                                                          CH.sub.3                                                                          --     2 (CH.sub.3).sub.2 CH(CH.sub.3).sub.2C                                                            Oil                                   120  CH.sub.3                                                                          t-C.sub.4 H.sub.9                                                                 --     2 CH.sub.3          Oil                                   121  CH.sub.3                                                                          t-C.sub.4 H.sub.9                                                                 --     2 (CH.sub.3).sub.2 CH                                                                             Oil                                   122  CH.sub.3                                                                          t-C.sub.4 H.sub.9                                                                 --     2 (CH.sub.3).sub.3 C                                                                              Oil                                   123  CH.sub.3                                                                          CH.sub.3                                                                          5-CH.sub.3                                                                           2 CH.sub.3          102                                   124  CH.sub.3                                                                          CH.sub.3                                                                          5-CH.sub.3                                                                           2 (CH.sub.3).sub.2 CH                                                                              88                                   125  CH.sub.3                                                                          CH.sub.3                                                                          5-CH.sub.3                                                                           2 (CH.sub.3).sub.3 C                                                                              103                                   126  CH.sub.3                                                                          CH.sub.3                                                                          5-CH.sub.3                                                                           2 (CH.sub.3).sub.2 CH(CH.sub.3).sub.2 C                                                           Oil                                   127  CH.sub.3                                                                          CH.sub.3                                                                          5-CH.sub.3                                                                           2                                                                                ##STR72##                                              128  CH.sub.3                                                                          CH.sub.3                                                                          6-CH.sub.3                                                                           2 CH.sub.3          Oil                                   129  CH.sub.3                                                                          CH.sub.3                                                                          6-CH.sub.3                                                                           2 (CH.sub.3).sub.2 CH                                                                             Oil                                   130  CH.sub.3                                                                          CH.sub.3                                                                          6-CH.sub.3                                                                           2 (CH.sub.3).sub.3 C                                                                               93                                   131  CH.sub.3                                                                          CH.sub.3                                                                          6-CH.sub.3                                                                           2 (CH.sub.3).sub.2 CH(CH.sub.3).sub.2 C                                                            68                                   132  CH.sub.3                                                                          CH.sub.3                                                                          6-CH.sub.3                                                                           2                                                                                ##STR73##        Oil                                   133  CH.sub.3                                                                          CH.sub.3                                                                          6-CH.sub.3                                                                           2 CH.sub.3 SCH.sub.2                                                                               93                                   134  CH.sub.3                                                                          CH.sub.3                                                                          6-CH.sub.3                                                                           2 C.sub.2 H.sub.5OCH.sub.2                                                                        Oil                                   135  CH.sub.3                                                                          CH.sub.3                                                                          6-CH.sub.3                                                                           2                                                                                ##STR74##        100                                   137  CH.sub.3                                                                          CH.sub.3                                                                          6-CH.sub.3                                                                           2                                                                                ##STR75##        Oil                                   138  CH.sub.3                                                                          CH.sub.3                                                                          6-CH.sub.3                                                                           2                                                                                ##STR76##        100                                   139  CH.sub.3                                                                          CH.sub.3                                                                          6-CH.sub.3                                                                           2                                                                                ##STR77##         52                                   139  CH.sub.3                                                                          CH.sub.3                                                                          6-CH.sub.3                                                                           2                                                                                ##STR78##         71                                   140  CH.sub.3                                                                          CH.sub.3                                                                          6-CH.sub.3                                                                           2                                                                                ##STR79##        Oil                                   141  CH.sub.3                                                                          CH.sub.3                                                                          6-CH.sub.3                                                                           2 (H.sub.3 COCH.sub.2).sub.3 C                                                                    108                                   142  CH.sub.3                                                                          CH.sub.3                                                                          6-CH.sub.3                                                                           2                                                                                ##STR80##        112                                   143  CH.sub.3                                                                          CH.sub.3                                                                          6-CH.sub.3                                                                           2                                                                                ##STR81##         83                                   144  CH.sub.3                                                                          CH.sub.3                                                                          6-CH.sub.3                                                                           2                                                                                ##STR82##        103                                   145  CH.sub.3                                                                          CH.sub.3                                                                          6-CH.sub.3                                                                           2                                                                                ##STR83##        110                                   146  CH.sub.3                                                                          CH.sub.3                                                                          6-CH.sub.3                                                                           2 CH.sub.2CH(CH.sub.2).sub.8                                                                      Oil                                   147  CH.sub.3                                                                          CH.sub.3                                                                          6-CH.sub.3                                                                           2                                                                                ##STR84##        Oil                                   148  CH.sub.3                                                                          CH.sub.3                                                                          6-CH.sub.3                                                                           2 (CH.sub.3).sub.3 -CH.sub.2                              149  CH.sub.3                                                                          CH.sub.3                                                                          6-CH.sub.3                                                                           2                                                                                ##STR85##        Oil                                   150  CH.sub.3                                                                          CH.sub.3                                                                          6-CH.sub.3                                                                           2                                                                                ##STR86##        118                                   151  CH.sub.3                                                                          CH.sub.3                                                                          6-CH.sub.3                                                                           2                                                                                ##STR87##        147                                   152  CH.sub.3                                                                          CH.sub.3                                                                          6-CH.sub.3                                                                           2                                                                                ##STR88##         88                                   153  CH.sub.3                                                                          CH.sub.3                                                                          6-CH.sub.3                                                                           2                                                                                ##STR89##         75                                   154  CH.sub.3                                                                          CH.sub.3                                                                          6-CH.sub.3                                                                           2                                                                                ##STR90##         98                                   155  CH.sub.3                                                                          CH.sub.3                                                                          6-CH.sub.3                                                                           2                                                                                ##STR91##        117                                   156  CH.sub.3                                                                          CH.sub.3                                                                          6-CH.sub.3                                                                           2                                                                                ##STR92##         84                                   157  CH.sub.3                                                                          CH.sub.3                                                                          6-CH.sub.3                                                                           2                                                                                ##STR93##         96                                   158  CH.sub.3                                                                          CH.sub.3                                                                          6-CH.sub.3                                                                           2                                                                                ##STR94##        125                                   159  CH.sub.3                                                                          CH.sub.3                                                                          6-CH.sub.3                                                                           2                                                                                ##STR95##        147                                   160  CH.sub.3                                                                          CH.sub.3                                                                          6-CH.sub.3                                                                           2                                                                                ##STR96##         98                                   161  CH.sub.3                                                                          CH.sub.3                                                                          6-CH.sub.3                                                                           2                                                                                ##STR97##        102                                   162  CH.sub.3                                                                          CH.sub.3                                                                          6-CH.sub.3                                                                           2                                                                                ##STR98##         83                                   163  CH.sub.3                                                                          CH.sub.3                                                                          6-CH.sub.3                                                                           2                                                                                ##STR99##        Oil                                   164  CH.sub.3                                                                          CH.sub.3                                                                          6-CH.sub.3                                                                           2                                                                                ##STR100##       103                                   165  CH.sub.3                                                                          CH.sub.3                                                                          6-CH.sub.3                                                                           2                                                                                ##STR101##       Oil                                   166  CH.sub.3                                                                          CH.sub.3                                                                          6-CH.sub.3                                                                           2                                                                                ##STR102##       Oil                                   167  Cl  Cl  6-Cl   2 CH.sub.3          123                                   168  Cl  Cl  6-Cl   2 (CH.sub.3).sub.3 C                                                                              172                                   169  Cl  CF.sub.3                                                                          6-F    2 (CH.sub.3).sub.3 C                                                                              122                                   170  Cl  CF.sub.3                                                                          6-Cl   2 CH.sub.3          133                                   171  Cl  CF.sub.3                                                                          6-Cl   2 (CH.sub.3).sub.3 C                                                                              128                                   172  i-C.sub.3 H.sub.7                                                                 i-C.sub.3 H.sub.7                                                                 6-i-C.sub.3 H.sub.7                                                                  2 CH.sub.3          125                                   173  i-C.sub.3 H.sub.7                                                                 i-C.sub.3 H.sub.7                                                                 6-i-C.sub.3 H.sub.7                                                                  2 (CH.sub.3).sub.3 C                                                                              178                                   174  CH.sub.3                                                                          F   6-CH.sub.3                                                                           2 CH.sub.3           85                                   175  CH.sub.3                                                                          F   6-CH.sub.3                                                                           2 (CH.sub.3).sub.3 C                                                                              110                                   176  CH.sub.3                                                                          CH.sub.3                                                                          6-F    2 CH.sub.3          Oil                                   177  CH.sub.3                                                                          CH.sub.3                                                                          6-F    2 (CH.sub.3).sub.3 C                                                                              Oil                                   178  CH.sub.3                                                                          t-C.sub.4 H.sub.9                                                                 6-CH.sub.3                                                                           2 CH.sub.3          109                                   179  CH.sub.3                                                                          t-C.sub.4 H.sub.9                                                                 6-CH.sub.3                                                                           2 (CH.sub.3).sub.2 CH                                                                              92                                   180  CH.sub.3                                                                          t-C.sub.4 H.sub.9                                                                 6-CH.sub.3                                                                           2 (CH.sub.3).sub.3 C                                                                              161                                   181  CH.sub.3                                                                          t-C.sub.4 H.sub.9                                                                 6-CH.sub.3                                                                           2 (CH.sub.3).sub.2 CHC(CH.sub.3).sub.2                                                             99                                   182  Cl  H   3.6-di-Cl                                                                            2 CH.sub.3          127                                   183  Cl  H   3.6-di-Cl                                                                            2 (CH.sub.3).sub.3 C                                                                              Oil                                   184  CH.sub.3                                                                          CH.sub.3                                                                          3.5-di-CH.sub.3                                                                      2 CH.sub.3          120                                   185  CH.sub.3                                                                          CH.sub.3                                                                          3.5-di-CH.sub.3                                                                      2 (CH.sub.3).sub.3 C                                                                              107                                   186  CH.sub.3                                                                          CH.sub.3                                                                          3.6-di-CH.sub.3                                                                      2 CH.sub.3          Oil                                   187  CH.sub.3                                                                          CH.sub.3                                                                          3.6-di-CH.sub.3                                                                      2 (CH.sub.3).sub.3 C                                                                               97                                   188  CH.sub.3                                                                          H   3.5.6-tri-CH.sub.3                                                                   2 CH.sub.3          Oil                                   189  CH.sub.3                                                                          H   3.5.6-tri-CH.sub.3                                                                   2 (CH.sub.3).sub.3 C                                                                               82                                   190  CH.sub.3                                                                          CH.sub.3                                                                          3-Br,6-CH.sub.3                                                                      2 CH.sub.3          Oil                                   191  CH.sub.3                                                                          CH.sub.3                                                                          3-Br,6-CH.sub.3                                                                      2 (CH.sub.3).sub.2 CH                                                                             Oil                                   192  CH.sub.3                                                                          CH.sub.3                                                                          3-Br,6-CH.sub.3                                                                      2 (CH.sub.3).sub.3 C                                                                              Oil                                   193  CH.sub.3                                                                          CH.sub.3                                                                          3-Br,6-CH.sub.3                                                                      2 (CH.sub.3).sub.2 CH C(CH.sub.3).sub.2                                                           Oil                                   194  CH.sub.3                                                                          CH.sub.3                                                                          tri-CH.sub.3                                                                         2 CH.sub.3          136                                   195  CH.sub.3                                                                          CH.sub.3                                                                          tri-CH.sub.3                                                                         2 (CH.sub.3).sub.2 CH                                                                              79                                   196  CH.sub.3                                                                          CH.sub.3                                                                          tri-CH.sub.3                                                                         2 (CH.sub.3).sub.3 C                                                                               98                                   __________________________________________________________________________

                                      TABLE 3                                     __________________________________________________________________________     ##STR103##                            (Ic)                                   Example No.                                                                          X  Y   Z.sub.n                                                                           m R.sup.2          M.p. °C.                          __________________________________________________________________________    197    Cl Cl  --  1 (CH.sub.3).sub.2 CH                                       198    Cl Cl  --  1                                                                                ##STR104##                                               199    Cl H   6-Cl                                                                              1 CH.sub.3                                                  200    Cl H   6-Cl                                                                              1 (CH.sub.3).sub.2 CH                                                                            115                                      201    Cl H   6-Cl                                                                              1 (CH.sub.3).sub.3CCH.sub.2                                                                       92                                      202    Cl H   6-Cl                                                                              1                                                                                ##STR105##                                               203    Cl H   6-Cl                                                                              1 (CH.sub.3).sub.2 CHCH.sub.2                                                                    Oil                                      204    Cl H   6-Cl                                                                              1                                                                                ##STR106##      Oil                                      205    Cl H   6-Cl                                                                              1                                                                                ##STR107##       80                                      206    Cl H   6-Cl                                                                              1                                                                                ##STR108##       46                                      207    Cl H   6-Cl                                                                              1                                                                                ##STR109##                                               208    CH.sub.3                                                                         CH.sub.3                                                                          5-CH.sub.3                                                                        1 (CH.sub.3).sub.2 CH                                       209    CH.sub.3                                                                         CH.sub.3                                                                          5-CH.sub.3                                                                        1 (CH.sub.3).sub.2 CHCH.sub.2                               210    CH.sub.3                                                                         CH.sub.3                                                                          5-CH.sub.3                                                                        1                                                                                ##STR110##                                               211    CH.sub.3                                                                         CH.sub.3                                                                          5-CH.sub.3                                                                        1                                                                                ##STR111##                                               212    CH.sub.3                                                                         CH.sub.3                                                                          5-CH.sub.3                                                                        1                                                                                ##STR112##                                               213    CH.sub.3                                                                         CH.sub.3                                                                          6-CH.sub.3                                                                        1 CH.sub.3         Oil                                      214    CH.sub.3                                                                         CH.sub.3                                                                          6-CH.sub.3                                                                        1 C.sub.2 H.sub.5  Oil                                      215    CH.sub.3                                                                         CH.sub.3                                                                          6-CH.sub.3                                                                        1 (CH.sub.3)CH      54                                      216    CH.sub.3                                                                         CH.sub.3                                                                          6-CH.sub.3                                                                        1 (CH.sub.3).sub.2 CHCH.sub.2                                                                    Oil                                      217    CH.sub.3                                                                         CH.sub.3                                                                          6-CH.sub.3                                                                        1                                                                                ##STR113##       95                                      218    CH.sub.3                                                                         CH.sub.3                                                                          6-CH.sub.3                                                                        1                                                                                ##STR114##      Oil                                      219    CH.sub.3                                                                         CH.sub.3                                                                          6-CH.sub.3                                                                        1                                                                                ##STR115##      Oil                                      220    CH.sub.3                                                                         CH.sub.3                                                                          6-CH.sub.3                                                                        1 (CH.sub.3).sub.3 C                                                                             Oil                                      221    CH.sub.3                                                                         CH.sub.3                                                                          6-CH.sub.3                                                                        1                                                                                ##STR116##       98                                      222    CH.sub.3                                                                         CH.sub.3                                                                          6-CH.sub.3                                                                        1 (CH.sub.3).sub.3 CCH.sub.2                                                                     Oil                                      223    CH.sub.3                                                                         CH.sub.3                                                                          6-CH.sub.3                                                                        1                                                                                ##STR117##                                               224    Cl Cl  --  2 (CH.sub.3).sub.2 CH                                       225    Cl Cl  --  2 (CH.sub.3).sub.2 CHCH.sub.2                               226    Cl Cl  --  2                                                                                ##STR118##                                               227    Cl Cl  --  2 C.sub.2 H.sub.5OC.sub.2 H.sub.4O C.sub.2 H.sub.4          228    Cl H   6-Cl                                                                              2 H.sub.3 C                                                 229    Cl H   6-Cl                                                                              2 (CH.sub.3).sub.2 CH                                                                            121                                      230    Cl H   6-Cl                                                                              2 (CH.sub.3).sub.2 CHCH.sub.2                                                                    108                                      231    Cl H   6-Cl                                                                              2                                                                                ##STR119##      100                                      232    Cl H   6-Cl                                                                              2                                                                                ##STR120##      Oil                                      233    Cl H   6-Cl                                                                              2                                                                                ##STR121##      Oil                                      234    Cl H   6-Cl                                                                              2                                                                                ##STR122##      138                                      235    CH.sub.3                                                                         CH.sub.3                                                                          5-CH.sub.3                                                                        2 H.sub.3 C                                                 236    CH.sub.3                                                                         CH.sub.3                                                                          5-CH.sub.3                                                                        2 (CH.sub.3).sub.2 CH                                       237    CH.sub.3                                                                         CH.sub.3                                                                          5-CH.sub.3                                                                        2 (CH.sub.3).sub.2 CHCH.sub.2                               238    CH.sub.3                                                                         CH.sub.3                                                                          5-CH.sub.3                                                                        2                                                                                ##STR123##                                               239    CH.sub.3                                                                         CH.sub.3                                                                          5-CH.sub.3                                                                        2                                                                                ##STR124##                                               240    CH.sub.3                                                                         CH.sub.3                                                                          5-CH.sub.3                                                                        2                                                                                ##STR125##                                               241    CH.sub.3                                                                         CH.sub.3                                                                          6-CH.sub.3                                                                        2 H.sub.3 C        105                                      242    CH.sub.3                                                                         CH.sub.3                                                                          6-CH.sub.3                                                                        2 C.sub.2 H.sub.5  102                                      243    CH.sub.3                                                                         CH.sub.3                                                                          6-CH.sub.3                                                                        2 (CH.sub.3).sub.2 CH                                                                            Oil                                      244    CH.sub.3                                                                         CH.sub.3                                                                          6-CH.sub.3                                                                        2 (CH.sub.3).sub.2 CHCH.sub.2                                                                    Oil                                      245    CH.sub.3                                                                         CH.sub.3                                                                          6-CH.sub.3                                                                        2                                                                                ##STR126##                                               246    CH.sub.3                                                                         CH.sub.3                                                                          6-CH.sub.3                                                                        2                                                                                ##STR127##      Oil                                      247    CH.sub.3                                                                         CH.sub.3                                                                          6-CH.sub.3                                                                        2                                                                                ##STR128##      Oil                                      248    CH.sub.3                                                                         CH.sub.3                                                                          6-CH.sub.3                                                                        2                                                                                ##STR129##      110                                      249    CH.sub.3                                                                         CH.sub.3                                                                          6-CH.sub.3                                                                        2 (CH.sub.3).sub.3 C                                                                             109                                      250    CH.sub.3                                                                         CH.sub.3                                                                          6-CH.sub.3                                                                        2                                                                                ##STR130##      Oil                                      251    CH.sub.3                                                                         CH.sub.3                                                                          6-CH.sub.3                                                                        2                                                                                ##STR131##      Oil                                      252    CH.sub.3                                                                         CH.sub.3                                                                          6-CH.sub.3                                                                        2 (CH.sub.3).sub.3 CCH.sub.2                                                                     Oil                                      253    CH.sub.3                                                                         CH.sub.3                                                                          6-CH.sub.3                                                                        2                                                                                ##STR132##      142                                      254    CH.sub.3                                                                         t-C.sub.4 H.sub.9                                                                 --  2                                                                                ##STR133##      Oil                                      255    CH.sub.3                                                                         F   6-CH.sub.3                                                                        2 (CH.sub.3).sub.2 CH                                                                            Oil                                      __________________________________________________________________________

EXAMPLE 256 ##STR134##

2.57 g (10 mmol) of3-(2,4,6-trimethyl-phenyl)-1,5-trimethylene-pyrrolidine-2,4-dione aresuspended in 50 ml of absolute THF (tetrahydrofuran), and dimethylamineis subsequently passed through until gas is taken up no longer. Afterthe THF has been removed on a rotary evaporator, the residue is dried invacuo at 70° C.

Yield: 2.69 g (89.7% of theory) m.p. 62° C.

In a corresponding manner, compounds of the formula (Id) were prepared:

                  TABLE 4                                                         ______________________________________                                         ##STR135##                   (Id)                                            Example No.                                                                             X      Y       Z.sub.n                                                                            m    λ.sup.⊕                                                                  M.p. °C.                      ______________________________________                                        257       CH.sub.3                                                                             CH.sub.3                                                                              CH.sub.3                                                                           1    Na.sup.⊕                                                                        <230                                 258       CH.sub.3                                                                             CH.sub.3                                                                              CH.sub.3                                                                           1    NH.sub.3.sup.⊕                                                                   228                                 ______________________________________                                    

INTERMEDIATES EXAMPLE 5' ##STR136##

223 g (1.125 mol) of mesityleneacetyl chloride are added dropwise at 0°to 10° C. to 182 ml (1.157 mol) of ethyl pipecolinate and 162 ml (1.157mol) of triethylamine in 1,200 ml of absolute tetrahydrofuran (THF),followed by stirring for 1 hour at room temperature. After the mixturehas been stirred into 5 liters of ice water and 500 ml of 1N HCl, theproduct is filtered off with suction, washed with water and dried invacuo at 50° C. over P₂ O₅. 342.3 g (95.2% of theory) of ethylN-(2,4,6-trimethylphenylacetyl)-piperidine-2-carboxylate are obtained.

EXAMPLE 37' ##STR137##

20 g (0.5 mol) of NaOH pellets are added to 115 g (1 mol) of L-prolinein 1 liter of water. 60 g (1.5 mol) of NaOH in 300 ml of water and 197.6g (1 mol) of mesityleneacetyl chloride are added dropwise in asynchronous manner at a temperature of less than 40° C., followed bystirring for 1 hour. The mixture is subsequently acidified at 5° to 20°C. using concentrated hydrochloric acid, and the product is filtered offwith suction and dried in vacuo at 70° C. over P₂ O₅.

Yield: 262 g (95.3% of theory) of N-2,4,6-trimethylphenylacetylprolinem.p. 156° C.

EXAMPLE 26' ##STR138##

137.5 g (0.5 mol) of N-2,4,6-trimethylphenylacetyl-proline are dissolvedin 500 ml of methanol. After 73 ml (0.55 mol) of dimethoxypropane and4.75 g (25 mmol) of p-toluenesulphonic acid monohydrate have been added,the mixture is refluxed for 2 hours. After the mixture has beenevaporated on a rotary evaporator, the residue is taken up in methylenechloride and washed using sodium hydrogen carbonate solution, and themethylene chloride phase is dried and evaporated on a rotary evaporator.After the residue had been recrystallized from methylenechloride/methyl-tert.-butyl ether/n-hexane, 107.9 g (74.7%) of methylN-(2,4,6-trimethylphenylacetyl)-pyrrolidine-2-carboxylate were obtained.M.p. 74° C.

The active compounds are suitable for combating animal pests, preferablyarthropods and nematodes, in particular insects and arachnids,encountered in agriculture, in forestry, in the protection of storedproducts and of materials, and in the hygiene field. They are activeagainst normally sensitive and resistant species and against all or somestages of development. The abovementioned pests include:

From the order of the Isopoda, for example, Oniscus asellus,Armadillidium vulgare and Porcellio scaber.

From the order of the Diplopoda, for example, Blaniulus guttulatus.

From the order of the Chilopoda, for example, Geophilus carpophagus andScutigera spec.

From the order of the Symphyla, for example, Scutigerella immaculata.

From the order of the Thysanura, for example, Lepisma saccharina.

From the order of the Collembola, for example, Onychiurus armatus.

From the order of the Orthoptera, for example, Blatta orientalis,Periplaneta americana, Leucophaea maderae, Blattella germanica, Achetadomesticus, Gryllotalpa spp., Locusta migratoria migratorioides,Melanoplus differentialis and Schistocerca gregaria.

From the order of the Dermaptera, for example, Forficula auricularia.

From the order of the Isoptera, for example, Reticulitermes spp..

From the order of the Anoplura, for example, Phylloxera vastatrix,Pemphigus spp., Pediculus humanus corporis, Haematopinus spp. andLinognathus spp.

From the order of the Mallophaga, for example, Trichodectes spp. andDamalinea spp.

From the order of the Thysanoptera, for example, Hercinothrips femoralisand Thrips tabaci.

From the order of the Heteroptera, for example, Eurygaster spp.,Dysdercus intermedius, Piesma quadrata, Cimex lectularius, Rhodniusprolixus and Triatoma spp.

From the order of the Homoptera, for example, Aleurodes brassicae,Bemisia tabaci, Trialeurodes vaporariorum, Aphis gossypii, Brevicorynebrassicae, Cryptomyzus ribis, Aphis fabae, Doralis pomi, Eriosomalanigerum, Hyalopterus arundinis, Macrosiphum avenae, Myzus spp.,Phorodon humuli, Rhopalosiphum padi, Empoasca spp., Euscelis bilobatus,Nephotettix cincticeps, Lecanium corni, Saissetia oleae, Laodelphaxstriatellus, Nilaparvata lugens, Aonidiella aurantii, Aspidiotushederae, Pseudococcus spp. and Psylla spp.

From the order of the Lepidoptera, for example, Pectinophoragossypiella, Bupalus piniarius, Cheimatobia brumata, Lithocolletisblancardella, Hyponomeuta padella, Plutella maculipennis, Malacosomaneustria, Euproctis chrysorrhoea, Lymantria spp. Bucculatrixthurberiella, Phyllocnistis citrella, Agrotis spp., Euxoa spp., Feltiaspp., Earias insulana, Heliothis spp., Spodoptera exigua, Mamestrabrassicae, Panolis flammea, Prodenia litura, Spodoptera spp.,Trichoplusia ni, Carpocapsa pomonella, Pieris spp., Chilo spp., Pyraustanubilalis, Ephestia kuehniella, Galleria mellonella, Tineolabisselliella, Tinea pellionella, Hofmannophila pseudospretella, Cacoeciapodana, Capua reticulana, Choristoneura fumiferana, Clysia ambiguella,Homona magnanima and Tortrix viridana.

From the order of the Coleoptera, for example, Anobium punctatum,Rhizopertha dominica, Acanthoscelides obtectus, Acanthoscelidesobtectus, Hylotrupes bajulus, Agelastica alni, Leptinotarsadecemlineata, Phaedon cochleariae, Diabrotica spp., Psylliodeschrysocephala, Epilachna varivestis, Atomaria spp., Oryzaephilussurinamensis, Anthonomus spp., Sitophilus spp., Otiorrhynchus sulcatus,Cosmopolites sordidus, Ceuthorrhynchus assimilis, Hypera postica,Dermestes spp., Trogoderma spp., Anthrenus spp., Attagenus spp., Lyctusspp., Meligethes aeneus, Ptinus spp., Niptus hololeucus, Gibbiumpsylloides, Tribolium spp., Tenebrio molitor, Agriotes.spp., Conoderusspp., Melolontha melolontha, Amphimallon solstitialis and Costelytrazealandica.

From the order of the Hymenoptera, for example, Diprion spp., Hoplocampaspp., Lasius spp., Monomorium pharaonis and Vespa spp..

From the order of the Diptera, for example, Aedes spp., Anopheles spp.,Culex spp., Drosophila melanogaster, Musca spp., Fannia spp., Calliphoraerythrocephala, Lucilia spp., Chrysomyia spp., Cuterebra spp.,Gastrophilus spp., Hyppobosca spp., Stomoxys spp., Oestrus spp.,Hypoderma spp., Tabanus spp., Tannia spp., Bibio hortulanus, Oscinellafrit, Phorbia spp., Pegomyia hyoscyami, Ceratitis capitata, Dacus oleaeand Tipula paludosa.

From the order of the Siphonaptera, for example, Xenopsylla cheopis andCeratophyllus spp..

From the order of the Arachnida, for example, Scorpio maurus andLatrodectus mactans.

From the order of the Acarina, for example, Acarus siro, Argas spp.,Ornithodoros spp., Dermanyssus gallinae, Eriophyes ribis, Phyllocoptrutaoleivora, Boophilus spp., Rhipicephalus spp., Amblyomma spp., Hyalommaspp., Ixodes spp., Psoroptes spp., Chorioptes spp., Sarcoptes spp.,Tarsonemus spp., Bryobia praetiosa, Panonychus spp. and Tetranychusspp..

The phytoparasitic nematodes include Pratylenchus spp., Radopholussimilis, Ditylenchus dipsaci, Tylenchulus semipenetrans, Heteroderaspp., Meloidogyne spp., Aphelenchoides spp., Longidorus spp., Xiphinemaspp. and Trichodorus spp..

The active compounds according to the invention can furthermore be usedas defoliants, desiccants, agents for destroying broad-leaved plantsand, especially, as weed-killers. By weeds, in the broadest sense, thereare to be understood all plants which grow in locations where they areundesired. Whether the substances according to the invention act astotal or selective herbicides depends essentially on the amount used.

It is characteristic of the compounds according to the invention thatthey have a selective activity against monocotyledon weeds when used inthe pre- and post-emergence method, while being well tolerated by cropplants.

The active compounds according to the invention can be used, forexample, in connection with the following plants:

Monocotyledon weeds of the genera: Echinochloa, Setaria, Panicum,Digitaria, Phleum, Poa, Festuca, Eleusine, Brachiaria, Lolium, Bromus,Avena, Cyperus, Sorghum, Agropyron, Cynodon, Monochoria, Fimbristylis,Sagittaria, Eleocharis, Scirpus, Paspalum, Ischaemum, Sphenoclea,Dactyloctenium, Agrostis, Alopecurus and Apera.

Monocotyledon cultures of the genera: Oryza, Zea, Triticum, Hordeum,Avena, Secale, Sorghum, Panicum, Saccharum, Ananas, Asparagus andAllium.

However, the use of the active compounds according to the invention isin no way restricted to these genera, but also extends in the samemanner to other plants.

The compounds are suitable, depending on the concentration, for thetotal combating of weeds, for example on industrial terrain and railtracks, and on paths and squares with or without tree plantings.Equally, the compounds can be employed for combating weeds in perennialcultures, for example afforestations, decorative tree plantings,orchards, vineyards, citrus groves, nut orchards, banana plantations,coffee plantations, tea plantations, rubber plantations, oil palmplantations, cocoa plantations, soft fruit plantings and hopfields, andfor the selective combating of weeds in annual cultures.

In this context, the active compounds according to the invention notonly have an excellent action against noxious plants but are also welltolerated by important crop plants, such as, for example, wheat, cotton,soya beans, citrus fruit and sugar beet, and they can therefore be usedas selective weedkillers.

The active compounds can be converted into the customary formulations,such as solutions, emulsions, powders, foams, suspensions, pastes,granules, aerosols, natural and synthetic materials impregnated withactive compound, very fine capsules in polymeric substances and incoating compositions for seed, furthermore in formulations using burningequipment, such as fumigating cartridges, fumigating cans, fumigatingspirals and the like, as well as ULV cold-mist and warm-mistformulations.

These formulations are produced in a known manner, for example by mixingthe active compounds with extenders, that is liquid solvents, liquefiedgases under pressure and/or solid carriers, optionally with the use ofsurface-active agents, that is emulsifying agents and/or dispersingagents and/or foam-forming agents. In the case of the use of water as anextender, organic solvents can, for example, also be used as auxiliarysolvents. As liquid solvents, there are suitable in the main: aromatics,such as xylene, toluene or alkylnaphthalenes, chlorinated aromatics orchlorinated aliphatic hydrocarbons, such as chlorobenzenes,chloroethylenes or methylene chloride, aliphatic hydrocarbons, such ascyclohexane or paraffins, for example petroleum fractions, alcohols,such as butanol or glycol as well as their ethers and esters, ketones,such as acetone, methyl ethyl ketone, methyl isobutyl ketone orcyclohexanone, strongly polar solvents, such as dimethylformamide anddimethyl sulphoxide, as well as water; liquefied gaseous extenders orcarriers are taken to mean those liquids which are gaseous at normaltemperature and under atmospheric pressure, for example aerosolpropellant, such as halogenohydrocarbons as well as butane, propane,nitrogen and carbon dioxide; as solid carriers there are suitable: forexample ground natural minerals, such as kaolins, clays, talc, chalk,quartz, attapulgite, montmorillonite or diatomaceous earth, and groundsynthetic minerals, such as highly disperse silica, alumina andsilicates, as solid carriers for granules there are suitable: forexample ,crushed and fractionated natural rocks such as calcite, marble,pumice, sepiolite and dolomite, as well as synthetic granules ofinorganic and organic meals, and granules of organic material such assawdust, coconut shells, corn cobs and tobacco stalks; as emulsifyingand/or foamforming agents there are suitable: for example,non-ionic andanionic emulsifiers, such as polyoxyethylene fatty acid esters,polyoxyethylene fatty alcohol ethers, for example, alkylaryl polyglycolethers, alkylsulphonates, alkyl sulphates, arylsulphonates as well asalbumen hydrolysis products; as dispersing agents there are suitable:for example, ligninsulphite waste liquors and methylcellulose.

Adhesives such as carboxymethylcellulose and natural and syntheticpolymers in the form of powders, granules or latexes, such as gumarabic, polyvinyl alcohol and polyvinyl acetate, as well as naturalphospholipids, such as cephalins and lecithins, and syntheticphospholipids, can be used in the formulations. Further additives can bemineral and vegetable oils.

It is possible to use colorants such as inorganic pigments, for example,iron oxide, titanium oxide and Prussian Blue, and organic dyestuffs,such as alizarin dyestuffs, azo dyestuffs and metal phthalocyaninedyestuffs, and trace nutrients such as salts of iron, manganese, boron,copper, cobalt, molybdenum and zinc.

The formulations in general contain between 0.1 and 95 per cent byweight of active compound, preferably between 0.5 and 90%.

The active compounds according to the invention can be present in theircommercially available formulations and in the use forms, prepared fromthese formulations, as a mixture with other active compounds, such asinsecticides, attractants, sterilizing agents, acaricides, nematicides,herbicides or fungicides. The insecticides include, for example,phosphates, carbamates, carboxylates, chlorinated hydrocarbons,phenylureas and substances produced by microorganisms, inter alia.

The active compounds according to the invention can furthermore bepresent in their commercially available formulations and in the useforms, prepared from these formulations, as a mixture with synergisticagents. Synergistic agents are compounds which increase the action ofthe active compounds, without it being necessary for the synergisticagent added to be active itself.

The active compound content of the use forms prepared from thecommercially available formulations can vary within wide limits. Theactive compound concentration of the use forms can be from 0.0000001 to95% by weight of active compound, preferably between 0.0001 and 1% byweight.

The compounds are employed in a customary manner appropriate for the useforms.

The active compounds which can be used according to the invention arealso suitable for combating mites, ticks etc. in the sector of animalkeeping and cattle breeding; better results, for example higher milkproduction, greater weight, more attractive animal pelt, longer lifeetc., can be achieved by combating the pests.

The application of the active compounds which can be used according tothe invention occurs in this sector in a known fashion, such as by oralapplication in the form of, for example, tablets, capsules, potions,granules, by means of dermal or external application in the form of, forexample, dipping, spraying, pouring-on, spotting-on and dusting, as wellas by means of parenteral application in the form, for example, ofinjection, and, furthermore, by means of the feed-through process. Inaddition, application as moulded articles (collar, ear tag) is alsopossible.

The compounds of the formula (I) according to the invention showantimicrobial, in particular powerful antibacterial antimycotic,actions. They possess a very broad spectrum of antimycotic action, inparticular against Dermatophytes and Blastomycetes, and biphasic fungi,for example against Candida species, such as Candida albicans,Epidermophyton species, such as Epidermophyton floccosum, Aspergillusspecies, such as Aspergillus niger and Aspergillus fumigatus,Trichophyton species, such as Trichophyton mentagrophytes, Microsporonspecies, such as Microsporon felineum, and also Torulopsis species, suchas Torulopsis glabrata. The enumeration of these microorganisms in nocase represents a limitation of the germs which can be combated, but isonly of illustrative character.

Examples of indications in human medicine which may be mentioned are:Dermatomycoses and systemic mycoses caused by Trichophytonmentagrophytes and other Trichophyton species, Microsporon species andalso Epidermophyton floccosum, Blastomycetes and biphasic fungi, andmoulds.

Indication areas which may be mentioned in veterinary medicine by way ofexample are: All dermatomycoses and systemic mycoses, in particularthose caused by the abovementioned pathogens.

The present invention includes pharmaceutical preparations whichcontain, beside non-toxic, inert pharmaceutically suitable excipients,one or more active compounds according to the invention, or whichconsist of one or more active compounds according to the invention.

The present invention also includes pharmaceutical preparations indosage units. This means that the preparations are present in the formof individual portions, for example tablets, coated tablets, capsules,pills, suppositories and ampoules, whose active compound contentcorresponds to a fraction or a multiple of an individual dose. Thedosage units may contain, for example 1, 2, 3 or 4 individual doses or1/2, 1/3, or 1/4 of an individual dose. An individual dose preferablycontains the amount of active compound which is administered in oneapplication and which usually corresponds to a whole, a half or a thirdor a quarter of a daily dose.

Non-toxic, inert, pharmaceutically suitable excipients are taken to meansolid, semi-solid or liquid diluents, fillers or formulation auxiliariesof any type.

Preferred pharmaceutical preparations which may be mentioned aretablets, coated tablets, capsules, pills, granules, suppositories,solutions, suspensions and emulsions, pastes, ointments, gels, creams,lotions, powders or sprays.

Tablets, coated tablets, capsules, pills and granules may contain theactive compound(s) in addition to the customary excipients, such as (a)fillers and extenders, for example, starches, lactose, sucrose, glucose,mannitol and silica, (b) binders, for example carboxymethylcellulose,alginates, gelatin, polyvinylpyrrolidone, (c) humectants, for example,glycerol, (d) disintegrants, for example, agar-agar, calcium carbonateand sodium bicarbonate, (e) solution retardants, for example, paraffin,and (f) absorption accelerators, for example, quaternary ammoniumcompounds, (g) wetting agents, for example cetyl alcohol, glycerolmonostearate, (h) adsorption agents, for example, kaolin and bentonite,and (i) lubricants, for example, talc, calcium stearate and magnesiumstearate and solid polyethylene glycols or mixtures of the substancesmentioned under (a) to (i).

The tablets, coated tablets, capsules, pills and granules may beprovided with the customary coatings and shells, which may optionallycontain opacifying agents, and they can be composed such that theyrelease the active compound(s) only, or preferably, in a certain part ofthe intestinal tract, if appropriate in a slow-release manner, examplesof embedding materials which can be used being polymeric substances andwaxes.

If appropriate, the active compound(s) can also be in amicroencapsulated form together with one or more of the abovementionedexcipients.

In addition to the active compound(s), suppositories may contain thecustomary water-soluble or water-insoluble excipients, for examplepolyethylene glycols, fats, for example cocoa fat, and higher esters(for example C₁₄ -alcohol with C₁₆ -fatty acid) or mixtures of thesesubstances.

Ointments, pastes, creams and gels may contain, besides the activecompound(s), the customary excipients, for example animal and vegetablefats, waxes, paraffins, starch, tragacanth, cellulose derivatives,polyethylene glycols, silicones, bentonites, silica, talc and zinc oxideor mixtures of these substances.

Powders and sprays may contain, besides the active compound(s), thecustomary excipients, for example, lactose, talc, silica, aluminiumhydroxide, calcium silicate and polyamide powder or mixtures of thesesubstances, and sprays may additionally contain the customarypropellants, for example, chlorofluoro hydrocarbons.

Solutions and emulsions may contain, besides the active compound(s), thecustomary excipients, such as solvents, solution retardants andemulsifiers, for example water, ethyl alcohol, isopropyl alcohol, ethylcarbonate, ethyl acetate, benzyl alcohol, benzyl benzoate, propyleneglycol, 1,3-butylene glycol, dimethylformamide, oils, in particularcottonseed oil, groundnut oil, corn germ oil, olive oil, castor oil andsesame oil, glycerol, glycerol formal, tetrahydrofurfuryl alcohol,polyethylene glycols and fatty acid esters of sorbitan or mixtures ofthese substances.

For parenteral application, the solutions and emulsions can also bepresent in sterile and blood-isotonic forms.

Suspensions can contain, besides the active compound(s), the customaryexcipients, such as liquid diluents, for example, water, ethyl alcohol,propyl alcohol, suspending agents, for example, ethoxylated isostearylalcohols, polyoxyethylene sorbitol esters and polyoxyethylene sorbitanesters, microcrystalline cellulose, aluminium metahydroxide, bentonite,agar-agar and tragacanth or mixtures of these substances.

The said formulation forms may also contain colorants, preservatives andodor- and flavor-improving additives, for example peppermint oil andeucalyptus oil, and sweeteners, for example, saccharin.

The therapeutically active compounds should preferably be present in theabovementioned pharmaceutical preparations in a concentration of about0.1 to 99.5, preferably of 0.5 to 95, % by weight of the total mixture.

The pharmaceutical preparations indicated above can also contain furtherpharmaceutical active compounds in addition to the active compoundsaccording to the invention.

The pharmaceutical preparations indicated above are prepared in acustomary manner by known methods, for example by mixing the activecompound(s) with the excipient(s).

The present invention also includes the use of the active compoundsaccording to the invention, and that of the pharmaceutical preparationscontaining one or more active compounds according to the invention, inhuman and veterinary medicine for the prophylaxis, amelioration and/orcure of the diseases indicated above.

The active compounds or the pharmaceutical preparations can beadministered locally, orally, parenterally, intraperitoneally and/orrectally, preferably parenterally, in particular intravenously.

In general, it has proved advantageous both in human and in veterinarymedicine to administer the active compound(s) according to the inventionin total amounts of about 2.5 to about 200, preferably from 5 to 150,mg/kg of body weight every 24 hours, if appropriate in the form ofseveral individual doses, to obtain the desired results.

For oral administration, the active compounds according to the inventionare administered in total amounts of about 2.5 to about 200, preferablyof 5 to 150, mg/kg of body weight every 24 hours, and for parenteralapplication in total amounts of about 2.5 to about 50, preferably of 1to 25, mg/kg of body weight every 24 hours.

It may be necessary, however, to deviate from the said dosages,depending upon the nature and the body weight of the subject to betreated, the nature and severity of the disease, the nature of thepreparation and the administration of the medicament and also the periodor interval within which the administration takes place. Thus, in somecases it may be sufficient to manage with less than the abovementionedamount of active compound, while in other cases the amount of activecompound indicated above must be exceeded. The optimum dosage requiredin each case and the nature of administration of the active compoundscan easily be established by anyone skilled in the art on the basis ofhis expert knowledge.

EXAMPLE A Tetranychus test (resistant)

Solvent: 7 parts by weight of dimethylformamide

Emulsifier: 1 part by weight of alkylaryl polyglycol ether.

To produce a suitable preparation of active compound, 1 part by weightof active compound is mixed with the stated amount of solvent and thestated amount of emulsifier, and the concentrate is diluted with waterto the desired concentration.

Bean plants (Phaseolus vulgaris) which are heavily infested with alldevelopment stages of the common spider mite or bean spider mite(Tetranychus urticae) are treated by being dipped into the activecompound preparation of the desired concentration.

After the desired time the destruction is determined in %. 100% heredenotes that all spider mites have been destroyed; 0% denotes that noneof the spider mites have been destroyed.

In this test, for example, the following compounds of the PreparationExamples show a superior activity compared with the prior art (88).

EXAMPLE B Pre-emergence test

Solvent: 5 parts by weight of acetone

Emulsifier: 1 part by weight of alkylaryl polyglycol ether.

To produce a suitable preparation of active compound, 1 part by weightof active compound is mixed with the stated amount of solvent, thestated amount of emulsifier is added and the concentrate is diluted withwater to the desired concentration.

Seeds of the test plants are sown in normal soil and, after 24 hours,watered with the preparation of the active compound. It is expedient tokeep constant the amount of water per unit area. The concentration ofthe active compound in the preparation is of no importance, only theamount of active compound applied per unit area being decisive. Afterthree weeks, the degree of damage to the plants is rated in % damage incomparison to the development of the untreated control. The figuresdenote:

0%=no action (like untreated control)

100%=total destruction

In this test, for example, the following compounds of the PreparationExamples show a superior activity compared with the prior art: (1),(13).

EXAMPLE C Post-emergence test

Solvent: 5 parts by weight of acetone

Emulsifier: 1 part by weight of alkylaryl polyglycol ether.

To produce a suitable preparation of active compound, 1 part by weightof active compound is mixed with the stated amount of solvent, thestated amount of emulsifier is added and the concentrate is diluted withwater to the desired concentration.

Test plants which have a height of 5-15 cm are sprayed with thepreparation of the active compound in such a way as to apply theparticular amounts of active compound desired per unit area. Theconcentration of the spray liquor is so chosen that the particularamounts of active compound desired are applied in 2,000 l of water/ha.After three weeks, the degree of damage to the plants is rated in %damage in comparison to the development of the untreated control. Thefigures denote:

0%=no action (like untreated control)

100%=total destruction

In this test, for example, the following compounds of the PreparationExamples show a superior activity compared with the prior art: (1),(13).

EXAMPLE D Test with Lucilia cuprina resistant larvae

Solvent:

35 parts by weight of ethylene glycol monomethyl ether

35 parts by weight of nonylphenol polyglycol ether.

To produce a suitable preparation of active compound, three parts byweight of active compound are mixed with seven parts by weight of theabovementioned mixture and the concentrate thus obtained is diluted withwater to the particular desired concentration.

About 20 Lucilia cuprina resistant larvae are introduced into a testtube which contains approx. 1 cm: of horse meat and 0.5 ml of thepreparation of active compound. After 24 hours, the degree ofdestruction is determined.

In this test, for example, the following compounds of the PreparationExamples show a highly pronounced activity: 7, 54, 58, 62, 64, 67, 68,213, 215, 216, 217, 222.

EXAMPLE E Test with Psoroptes ovis

Emulsifier:

35 parts by weight of ethylene glycol monomethyl ether

35 parts by weight of nonylphenol polyglycol ether.

To produce a suitable preparation of active compound, three parts byweight of active compound are mixed with seven parts by weight of theabovementioned mixture, and the concentrate thus obtained is dilutedwith water to the desired concentration.

About 10-25 Psoroptes ovis are introduced into 1 ml of the activecompound preparation to be tested, which has been pipetted into tabletnests of a deep-drawn pack. After 24 hours, the degree of destruction isdetermined.

In this test, for example, the following compounds of the PreparationExamples show a highly pronounced activity: 39, 55, 57, 62, 87, 89, 167,201, 245.

EXAMPLE F Antimycotic in vitro activity Description of the test

The in vitro tests were carried out using microorganism inocular havingan average of 1×10⁴ microorganisms/ml of substrate. The nutrient mediumused was Yeast Nitrogen Base medium for yeasts and Kimmig medium formoulds and Dermatophytes.

The incubation temperature was 37° C. in the case of the yeasts and 28°C. in the case of molds and Dermatophytes, the incubation time was 24 to96 hours for yeasts and 96 to 120 hours for Dermatophytes and molds.

The fungicides were assessed by plating and reincubation of completelyinhibited batches, fungicidal concentrations being those which containfewer than 100 microorganisms c.f.n. (colony-forming unit) per ml.

In this test, the compounds of the formula (I) according to theinvention, of the Preparation Examples 36, 40, 85, 91, 114, 116, 120,167, 170, 174, 176, 178, 182, 184, 188, 194 show a highly pronouncedantimycotic activity.

It will be appreciated that the instant specification and claims are setforth by way of illustration and not limitation, and that variousmodifications and changes may be made without departing from the spiritand scope of the present invention.

What is claimed is:
 1. An acylamino acid ester of formula II ##STR139##wherein X is C₁ -C₆ -alkyl, or halogen,Y is hydrogen, C₁ -C₆ -alkyl,halogen, or C₁ -C₃ -halogenalkyl, Z is C₁ -C₆ -alkyl, or halogen, n is 0to 3, provided that when n is 0, Y is not hydrogen, and R³ is C₁ -C₆-alkyl.